Among women with invasive epithelial ovarian cancer, patients having a germline (gene change in a reproductive cell that could be passed to offspring) mutation in the BRCA1 or BRCA2 genes was associated with improved 5-year overall survival, with BRCA2 carriers having the best prognosis, according to a study in the January 25 issue of JAMA.
“Germline mutations in the tumor suppressor genes BRCA1 and BRCA2 are the strongest known genetic risk factors for both breast and epithelial ovarian cancer (EOC) and are found in 6 percent to 15 percent of women with EOC,” according to background information in the article. “The relative prognosis of BRCA1/2 carriers and noncarriers is unclear.”
Kelly L. Bolton, Ph.D., of the National Cancer Institute, Bethesda, Md., and colleagues conducted a study to provide evidence of the relative effect of germline BRCA1 and BRCA2 mutations on prognosis for women with epithelial ovarian cancer. The study consisted of a pooled analysis of 26 observational studies on the survival of women with ovarian cancer, which included data from 1,213 EOC cases with pathogenic germline mutations in BRCA1 (n = 909) or BRCA2 (n = 304) and from 2,666 noncarriers recruited and followed up at variable times between 1987 and 2010. During the 5 years following EOC diagnosis, 1,766 deaths occurred.
The researchers found that 5-year overall survival was 36 percent for noncarriers of the gene mutations, 44 percent for BRCA1 carriers, and 52 percent for BRCA2 carriers. In a model only adjusted for study site and year of diagnosis, BRCA1 carriers had a more favorable survival than noncarriers, which improved slightly after additional adjustment for stage, grade, histology, and age at diagnosis. BRCA2 carriers had a greater survival advantage compared with noncarriers, particularly after adjusting for other prognostic factors.
The survival advantage for BRCA1 and BRCA2 carriers compared with noncarriers was present but less marked among women who reported a family history of ovarian, breast cancer, or both.
Cigarette smoking and the risk of invasive epithelial ovarian cancer in a prospective cohort study
Few cohort studies have examined the association between cigarette smoking and ovarian cancer risk, either overall, or by histological subtype. In relation to the latter, it has been suggested that mucinous ovarian tumours may be aetiologically unrelated to the other types of epithelial tumours and that their respective associations with cigarette smoking may differ. We examined the association between smoking and ovarian cancer risk using data from participants in a randomised controlled trial of screening for breast cancer involving 89,835 women aged 40–59 years at recruitment. Cox proportional hazards models were used to estimate rate ratios (RR) and 95% confidence intervals (CI). During an average of 16.5 years of follow-up, we observed 454 incident cases of ovarian cancer (184 serous, 67 endometrioid, 32 mucinous, 171 other or unknown). We found that women who had smoked for several decades had an approximately two-fold increased risk of epithelial ovarian cancer. Relative to never-smokers, women who had smoked for 40 years or more were at the highest risk (RR=2.50, 95% CI=1.37–4.56). The association with non-mucinous tumours was similar to that observed overall. For mucinous tumours, a two-fold increased risk was observed with smoking of shorter duration, although the number of mucinous tumours in our data-set was small. Long-term cigarette smoking may be associated with an increased risk of epithelial ovarian tumours.
Department of Epidemiology and Social Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Room 1301, Bronx, NY 10461, USA
Corresponding Author InformationCorresponding author. Tel.: +1-718-430-3038; fax: +1-718-430-8653
“Our study results have potentially important implications for the clinical management of patients with EOC. Most immediately, our findings can be used by health care professionals for patient counseling regarding expected survival. BRCA1 and BRCA2 carriers with EOC respond better than noncarriers to platinum-based chemotherapies and have improved survival despite the fact that the disease is generally diagnosed at a later stage and higher grade. If patients could be stratified based on their BRCA status, their treatment could be tailored to reflect this, with noncarriers targeted for more aggressive treatments. Our data provide further support that there may be different functional mechanisms involved in the etiology of different subtypes of EOCs and, therefore, different therapeutic targets based on germline and somatic [changes to the genetics of a multicellular organism which are not passed on to its offspring through the germline] genetic variation,” the researchers write.
“… given the important prognostic information provided by BRCAl and BRCA2 status and the potential for personalized treatment in carriers, the routine testing of women presenting with high-grade serous EOC may now be warranted.”
Breast cancer is fairly common. One in nine Australian women will develop breast cancer before the age of 85. Many women have someone in their family who has had breast cancer; this can happen by chance, as the disease is so common. Family history becomes more important when there are more relatives with breast cancer on the same side of the family, especially if the cancer occurs at an early age. Most women will not develop breast cancer, even if they have a close relative with breast cancer.
Rarely, breast cancer can be caused by a fault in a gene that can be passed within families from one generation to another. These gene faults (mutations) can be inherited from either the mother’s or father’s side of the family. Less than 5% of all breast cancer cases are caused by an inherited gene fault.
Ovarian cancer is less common than breast cancer. One in 78 women will develop invasive epithelial ovarian cancer before the age of 85. Ovarian cancer sometimes has an association with breast cancer. The same inherited genetic faults that make a person more likely to develop breast cancer may also make a person more likely to develop ovarian cancer. Hereditary links appear to account for around 15% of all cases of invasive epithelial ovarian cancer. Women with a family history of breast cancer or ovarian cancer may be at increased risk of developing these cancers, with the risk increasing the more relatives are affected (with breast and/or ovarian cancer) on one side of the family.
National Breast and Ovarian Cancer Centre (NBOCC)
(JAMA. 2012;307:382-390. Available pre-embargo to the media at http://www.jamamedia.org)
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Editorial: Unwrapping the Implications of BRCA1 and BRCA2 Mutations in Ovarian Cancer
David M. Hyman, M.D., and David R. Spriggs, M.D., of Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, write in an accompanying editorial that the data from this study have important implications for the future of ovarian cancer research and treatment.
“Phase 3 studies that do not stratify by BRCA mutation status or account for this factor in a preplanned statistical analysis risk possible confounding because approximately 15 percent of unselected patients with serous ovarian cancer will carry germline BRCAl/2 mutations. Moreover, other studies have found differences in chemotherapy responsiveness and progression-free survival between sporadic BRCAl -and BRCA2-associated ovarian cancers. Germline BRCA testing needs to be consistently incorporated into both the routine management and future phase 3 trials of ovarian cancer.”
(JAMA. 2012;307:408-410. Available pre-embargo to the media at http://www.jamamedia.org)
Editor’s Note: Please see the article for additional information, including financial disclosures, funding and support, etc.
Source: American Medical Association (AMA)